The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes

Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.     

Seizure control in patients with idiopathic generalized epilepsies: EEG determinants of medication response

In a minority of patients with idiopathic generalized epilepsies (IGEs), seizures continue despite appropriate treatment. We sought to determine the clinical and EEG factors associated with medication response in these patients. All patients with IGEs evaluated by epilepsy specialists between 17 November 2008 and 16 November 2009 were included. We collected information on seizure freedom (dependent variable), EEG asymmetries, response to valproic acid (VPA), MRI characteristics, medication use, demographics, and seizure history (predictors). We identified 322 patients with IGEs; 45 (14%) were excluded from analyses because they had always had a normal EEG (N = 26), there were no EEG data (N = 3), or they were non-compliant with medication (N = 26). Patients with juvenile myoclonic epilepsy were more likely to respond to VPA than were patients with other IGEs, and VPA response was associated with seizure freedom. When EEG characteristics were considered, presence of any focal EEG abnormalities (focal slowing, focal epileptiform discharges, or both) was associated with decreased odds of seizure freedom. These findings suggest that patients with IGEs with poor seizure control may have atypical IGEs with possibly focal, for example, frontal, rather than thalamic onset.     

Effects of Application of Recycled Chicken Manure and Spent Mushroom Substrate on Organic Matter,Acidity, and Hydraulic Properties of Sandy Soils

Soil organic matter is a key resource base for agriculture. However, its content in cultivated soils is low and often decreases. This study aimed at examining the effects of long-term application of chicken manure (CM) and spent mushroom substrate (SMS) on organic matter accumulation, acidity, and hydraulic properties of soil. Two podzol soils with sandy texture in Podlasie Region (Poland) were enriched with recycled CM (10 Mg ha⁻¹) and SMS (20 Mg ha⁻¹), respectively, every 1–2 years for 20 years. The application of CM and SMS increased soil organic matter content at the depths of 0–20, 20–40, and 40–60 cm, especially at 0–20 cm (by 102–201%). The initial soil pH increased in the CM- and SMS-amended soil by 1.7–2.0 units and 1.0–1.2 units, respectively. Soil bulk density at comparable depths increased and decreased following the addition of CM and SMS, respectively. The addition of CM increased field water capacity (at –100 hPa) in the range from 45.8 to 117.8% depending on the depth within the 0–60 cm layer. In the case of the SMS addition, the value of the parameter was in the range of 42.4–48.5% at two depths within 0–40 cm. Depending on the depth, CM reduced the content of transmission pores (>50 µm) in the range from 46.3 to 82.3% and increased the level of residual pores (<0.5 µm) by 91.0–198.6%. SMS increased the content of residual pores at the successive depths by 121.8, 251.0, and 30.3% and decreased or increased the content of transmission and storage pores. Additionally, it significantly reduced the saturated hydraulic conductivity at two depths within 0–40 cm. The fitted unsaturated hydraulic conductivity at two depths within the 0–40 cm layer increased and decreased in the CM- and SMS-amended soils, respectively. The results provide a novel insight into the application of recycled organic materials to sequester soil organic matter and improve crop productivity by increasing soil water retention capacity and decreasing acidity. This is of particular importance in the case of the studied low-productivity sandy acidic soils that have to be used in agriculture due to limited global land resources and rising food demand.     

C–C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation

Background: Vitamin D (VD) deficiency results in a worse prognosis in patients with chronic lymphocytic leukemia (CLL) and may affect the production of cytokines. Nonetheless, there is the lack of studies dealing with VD supplementation and its impact on chemokines in CLL patients.

Aim: The primary endpoint of our interventional study was to evaluate the effect of cholecalciferol supplementation on serum chemokines levels in CLL patients.

Materials and methods: Eighteen subjects with CLL were enrolled for the study. Six-month-long cholecalciferol supplementation was performed in CLL patients with serum 25-OH-D₃ levels below 30?ng/ml. Cytokines levels were assessed at the beginning of the study and after 6 months. Baseline measurements of cytokines were compared to those in apparently healthy controls.

Results: Increased levels of CCL2, CCL3, CCL4, CXCL8, CXCL10, TNFα, bFGF, G-CSF, and VEGF were found in CLL patients in comparison with the healthy controls. In the course of the VD supplementation a decrease in serum levels of chemokines CCL11, CCL3, and cytokine PDGF-BB was observed. The decrease of CCL11 was found in CLL patients on VD supplementation solely, whereas the decrease of CCL3 and PDGF-BB was observed in CLL subjects on both chemotherapy and VD supplementation.

Conclusion: The VD supplementation may exert beneficial effect on chemokines levels in CLL patients with VD deficiency.     

Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers

BACKGROUND: Left ventricular (LV) diastolic dysfunction has been observed in cigarette smokers with coronary artery disease. The aim of the study was to assess LV and right ventricular (RV) diastolic function in healthy, young, and slim smokers before and after smoking one cigarette. MATERIAL AND METHODS: The participants were 66 healthy volunteers (age < 40 years; body mass index < 25 kg/m(2)): 33 smokers (study group [HS]) and 33 nonsmokers (control group). Echocardiographic examination was done in the HS before smoking one cigarette (HS-1) and after smoking one cigarette (HS-2). To assess diastolic function of LV and RV mitral valve flow (MVF), pulmonary venous flow (PVF) and tricuspid valve flow (TVF) were evaluated. RESULTS: MVF early to late phase ratio (E/A) was significantly lower in HS-1 and HS-2 than in the control group. The PVF systolic to diastolic phase ratio (S/D) was significantly higher in HS-1 and HS-2 than in the control group. These changes suggest LV diastolic function impairment in the HS, but the MVF pattern remained within the normal range. PVF S/D showed systolic dominance (S/D > 1) typical for impaired LV relaxation and abnormal for this age group. TVF E/A was significantly lower in HS-2 than in HS-1 and control subjects and suggests RV diastolic dysfunction. CONCLUSIONS: The following conclusion are made: (1) MVF and PVF demonstrate LV relaxation impairment in healthy smokers before and after smoking one cigarette; (2) the assessment of PVF is a good method reflecting LV diastolic function changes, even when MVF remains normal; and (3) TVF shows RV relaxation impairment after smoking one cigarette in healthy smokers.     

Eicosanoids in exhaled breath condensate and BAL fluid of patients with sarcoidosis

BACKGROUND: Measurement of inflammatory mediators in exhaled breath condensate (EBC) is an easy and noninvasive diagnostic method, which has gained popularity in the past few years. However, the source of these mediators is not precisely defined. It has been only presumed that inflammatory cells present in the airway lumen are the main source. Therefore, the aim of this study was to verify the relationship between EBC and BAL fluid (BALF) eicosanoids, and the percentage, number, and activity of cells in BALF. METHODS: In 28 sarcoidosis patients and 17 healthy subjects, 8-isoprostane, cysteinyl leukotrienes (CysLTs), and leukotriene B4 (LTB4) were measured in EBC by enzyme immunoassay. Eicosanoids were also examined in BALF in the study group. Cell count, percentage, and superoxide production by BALF cells were estimated. RESULTS: The mean (+/- SEM) CysLT and 8-isoprostane concentrations were higher in the sarcoidosis group (6.5 +/- 0 vs 27.82 +/- 6.65 pg/mL, respectively; and 2.67 +/- 0.16 vs 13.95 +/- 2.59 pg/mL, respectively). There were positive correlations between EBC and BALF 8-isoprostane concentration (r = 0.68, p < 0.0001) and LTB4 concentration (r = 0.43; p = 0.026). EBC LTB4 levels correlated with the number of lymphocytes per milliliter of BALF. The percentage and number of eosinophils in BALF correlated with EBC 8-isoprostane and BALF CysLT concentrations. No positive correlation was found between concentrations of EBC eicosanoids and percentages BALF lymphocytes, BALF macrophages, or superoxide production. CONCLUSIONS: The levels of 8-isoprostane and CysLT are elevated in EBC in sarcoidosis patients; however, a lack of correlation with BALF lymphocyte percentage does not encourage us to recommend the measurement of eicosanoids as activity markers. The positive correlation of EBC 8-isoprostane and BALF CysLT concentrations with the percentage of eosinophils in BALF, and the higher percentage of eosinophils in BALF from patients with grade 3 sarcoidosis, may suggest the possible prognostic value.